Our studies initially focused on patients with CD4 counts above 200 cells/mm3, administering IL-2 for 5 days approximately every 2 months at doses ranging from 6 to 18 million units/d. The courses of IL-2 were well-tolerated, although most of the patients required dosage reductions due to IL-2 related adverse effects. Sustained improvement in CD4 number was seen primarily in patients with greater than 200 CD4 cells/mm3. There also was a transient increase in viral load as measured by the bDNA assay seen at day 6 to day 8 following initiation of IL-2 therapy. Responses in CD4 number were less common in patients with lower baseline CD4 counts. Based on the preliminary results seen in our open trial, we undertook a 60 patient randomized trial to evaluate IL-2 therapy in patients with CD4 counts above 200 cells/mm in combination with currently approved antiretroviral therapies. This study also showed in a controlled setting that intermittent therapy with IL-2 can lead to a substantial and sustained increase in CD4 cell counts without leading to an increase in plasma viral load. We have improved the tolerance of IL-2, by decreasing the dose and duration of therapy, and by evaluating alternative methods of administering IL-2. We continued to follow patients receiving IL-2 to determine the long term side effects and immunologic activity of IL-2. Additional studies have shown that IL-2 leads to increased survival of CD4 cells, and this increased survival correlates with the increase in CD4 cell number following IL-2 therapy. During the past year, two phase 3 randomized, controlled trials (ESPRIT and SILCAAT) which were designed to examine the efficacy of IL-2 in decreasing the frequency of clinical endpoints, especially death and AIDS-related complications, were completed. Both studies showed similar results, that IL-2 does not provide any added clinical benefit over that seen with anti-retroviral therapy alone. Based on these studies, we have discontinued administration of any additional IL-2 cycles, have discontinued enrollment of any new patients into our IL-2 studies, and are in the process of closing our IL-2 protocols.